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Right. Um I'll see if I can care of my screen here. Uh It's just getting this going. I put that on. Okay. Right. Can you all see this first screen? Yes, we can. Ok. Wonderful. Okay. So, um as you heard about 23 times now, because I've given about 23 24 lectures this, this year. Um I'm Doctor John Vogel. I'm a recently retired consult, any Chris consultant in intensive care medicine and anaesthetics. And I've been trying to teach some of the more basic principles of physiology and how they are applied at the clinical arena and how, you know, the bedside. And I, we do that a lot and um we find that a lot of students sort of skip over this because it's something you have to do to get through, but they don't realize this is the stuff we need to use. So, a lot of the principles are not well explained. So that's what I've been trying to do for the last year or so. Um So today I want to talk about fluids and how they're used in severely fill. Um and uh I'll try not to focus too much on the detail that you can get from any book. And it's also quite fluid in that. They're a lot, there's a lot of debate and a lot of discussion about some of the things I'm about to tell you. So it's not cut and dry, but I'll try and give you some practical tips as well that are often in the textbooks. Okay. So today we're going to talk about the key role that fluids have and the model that I've uh I've been pushing is the model of oxygen delivery as being the main goal of what we're doing and how it's various components can be acted upon and how they interact with each other. So I gave an entire lecture on that and I always refer back to that model because it's a very good model to help you get out of trouble if you're ever in a very chaotic situation and you're not certain what to do first, just think of the three factors, okay, the physiology of fluid spaces. And I'll go into that in a little bit of detail cause I think it's often misunderstood. In fact, there was a recent paper by a series of very well known nephrologist, the United States who said that a paper by about four or five of them saying that medical students and senior doctors often misunderstand a lot of the concepts of physical, of the physiology of fluid spaces. Where would the fluids go? What about the vital role of the Glyco Calix. We talked briefly about that last year, but I'm going to reinforce just the aspects that to do with fluid and it's compartmentalization, the types of fluids we used whether the saline balanced salt solutions, keloids. And then we'll talk about some practical tips that are often um missed or misunderstood or not even applied. So oxygen delivery, as we said, I'm always referring back to this, this model, this paradigm because I think it's so important to really just simplify things when they get a bit too chaotic. Don't forget it's cardiac output, times your hemoglobin, times your oxygen saturation. If those three factors are okay, you're okay. You've done everything you can and how do you maximize cardiac output fluids, hemoglobin, well, red cells and oxygen saturation, oxygen. But today we're going to talk about fluids and how they impact on cardiac output. So the US Red Cross for years and years and years used to have a campaign, a publicity campaign or an advertising campaign rather. And it said something but they got it wrong. What did they say? They said blood saves lives. Hence they were asking people to donate blood but they got it wrong because it wasn't blood saves lives. According to the ex editors of the New England Journal Medicine, they said it should have said blood volume saves lives, not blood but blood volume. And this, according to this famous or well known uh professor of medicine. The most important discovery was the realization that anemia is well tolerated, provided blood volume is maintained. So it's blood volume accounts. So let's go over some very basic physiology of fluid spaces. So where do fluids go? Now, this is going to be a little bit of a simplistic model, but I think it's helps to refer back to this. So the total body water of somebody who say 70 kg is of the order of magnitude of 45 liters. It's not exact figure, but it's something of that order of magnitude. So let's say 45 liters and that 45 liters of total body water is divided up into compartments and the compartments are determined by membranes and those membranes will be permeable or impermeable the various substances. So the intracellular space which constitutes the vast majority of the total body water. You have more space in your cells than you do outside your cells. That's 30 liters of the 45 liters your extracellular space therefore is going to be 15 liters, 30 plus 15 is 45. That's your total body water. Now, the extracellular space can also be divided up and the intravascular spaces, three liters. Now be careful. We're not saying that you have three liters of blood of volume were saying it's three liters of fluid because we're considering that the red cells and white cells and platelets that would constitute about 45% of your uh intervascular space, let's say two out of 32 or the five liters that's intracellular. Okay. So it's all about extra cellular, not red cells or white cells. So basically talk about serum and plasma. That's about three liters of the 15 liters and your interstitial space. That's the fluid outside your vascular system. But outside your cells is about 12 readers. So let's go over it. 45 liters is a total third of that 45 liters, 30 is your intracellular, 15 extracellular of the extracellular is 12 is interesting Juul and about three liters as intra vascular. So as I said, there are membranes that determine where the fluid goes and that depends on what constitutes the elements making up that fluid. So for example, if I were to infuse one leader into someone's vein, so it's intravascular, how much would stay in? Well, that depends on what the fluid's made of. So if it's dextrose, 5% dextrose, let's say because um it's going to go through the entire system because there's nothing stopping it, there's no barrier, stopping the water and dextrose school right across from the intravascular to the interstitial to the intracellular space. That means of the leader, only about 70 mL will stay intervascularly. Now, you can work this out. It's just a matter of taking a proportion. Okay. But those were saying really is that very, very little uh water in the form of dextrose, 5% infused into a vessel will stay in the vessel. So if you're ever going to resuscitate somebody who was hypothalamic from blood loss using dextrose would not make a lot of sense because you're gonna need a lot of dextrose to, to fill the intravascular space. The next would be crystalloids and crystalloids, our salt containing solutions now because they have soul sodium and chloride and various proportions, they cannot get through the inter cellular membrane, so they stay outside the cellular space. So they will traverse the intravascular space and go into the interstitial space and proportionately, it means of a leader that's infused into a blood vessel only about a quarter, about quarter. So about 200 to 250 minutes, it'll state intravascularly and in the ideal world. And this is a bit idealized if you give a coal oid, say a large molecule like a protein like album in for example, that will not passed in theory, this is the intervascular um barrier. So it stays entirely in the intervascular space. So in terms of the efficiency of filling someone's intervascular space, in theory, um keloids would be the best because they will stay intravascular crystalloids will be the next best because most of it will go into the interstitial space, but a quarter at least will stay intervascularly and dextrose would not be very efficient because only about 70 mils of a leader, don't forget we're refusing a leader. Now uh would stay intravascularly. Most of it would go into cellular because it goes across the entire entire uh spectrum of spaces. So let's look at one of many studies and this is just looking at what the difference between crystalloid and college would be in terms of if you infuse it intravenously and, and see what it does to the blood volume. And this just confirms what I just said. So crystalloid, there's that is the amount of crystalloid that stays intravascularly. So how much the bloodline increases after a leader of crystalloid? And you can see a colloid which would be much greater in uh volume intravascular because it doesn't leak out as readily. But you can see over time it does come down. So a major fluid player that is often ignored and they explain a lot of what some of the controversies are and I'll come onto these controversies in a second is something called the Glyco Calix look like or what you may or may not have heard of this. So this is going to be taking me at least back to my medical student days because we were all taught and you probably may have been taught as soon. The what we call the Starlings single vascular barrier theory. And what does this say? It says that you haven't read the intravascular space, you have the green um endothelium which acts as a barrier and you have the interstitial space and you have hydrostatic pressure inside the vessel forcing fluid out. So that's a trans you date into the interstitial space. So there's a flow of fluid from the intravascular to the interstitial space. But to counteract that, so you don't dry, your introduced your space out, you have collide osmotic pressure, CLP, collide osmotic pressure of which 80% is constituted by albumin. And that will have an effect of sucking fluid back in to the intervascular space. And I remember as a medical student, I used to have to, I used to didn't have to, but I used to memorize the pressure is going out and the pressure is sucking fluid back in. And that was the way you know, we were taught and that was seemed to make sense. And that's um best theory has been around for a long time, hundreds years. But something's wrong with this theory. And if you can't explain every phenomenon with a with a hypothesis, you have to ask your question is the hypothesis correct. And what they found in experimental studies that even when you made the collide asthmatic pressure on the inside and outside the vessel equal, there was still fluid being drawn in by colli collide osmotic pressure. Now that not to happen because they were equal on both sides. Now, this is going to be a somewhat simplistic view. The real story is very much more complex. I could explain it to you someday, but this is a very good way of starting off at least gets you in the ballpark, it's not wrong. By the way, it's just that it's more, a little bit more involved. So um this is not the full story, but it's pretty close anyway. So here's a cartoon, there's your intervascular space and the dots represent album in the main constituent of called osmotic pressure. There's your endothelial cells, there's your interstitial space. As you can see the density of the keloids of the album on both sides are pretty similar. So let's say they're equal. So why is fluid being drawn into the intervascular space? If the, if the concentrations the same on both sides, that should not happen. Well, the reason it happens is because it's missing one vital element and that vital element that was only discovered. Well, it's not true. It was only discovered about a couple of decades ago was the Glyco Calix. Now, the Glyco Calix is made up of fine filaments. If you want to call them that, that are like little hairs. And you'll see in a second on electoral micrograph that are uh protein protein, it'd go like uh Glyco proteins or proteoglycan or sme know glycan. And these are filaments that are basically triggers and proteins and they trap if you like where they adhere, uh they, they attract album int into the between the filaments. So you have a very high concentration of albumin in that meshwork of the Glyco Calix. And so that's where the concentration grade it is between the interstitial space which is relatively um sparse. And the Glyco okay Alex where it's got a very dense, dense uh concentration of, of album. And so even if the albumin and inside the vessel and outside are equal, it doesn't matter as long as the Glyco Calix is intact because it will suck fluid into um into that very highly concentrated area. And then it will carry on into the intravascular space and then be dragged along with the blood as it flows downstream. So as long as your Glyco Calix is intact, then you will maintain that barrier, keeping fluid in the vessel because you'll still have called osmotic pressure. If the Glyco Calix is destroyed, on the other hand, that's different. Now, fluid will leak out and therefore you will not maintain your intravascular space as, as as well as if you have an intact like okay Alex things that destroy the Glyco okay, Alex are numerous but mainly things like uh inflammation. Um uh yes, chemically, profusion injuries and you'll see another one that's important in a second. And this is what it actually looks like in case you wondered if it actually exists or not and you can see these little filaments or these hairs if you like within them are large, many molecules of album in which was that vascular barrier, they call that the endovascular barrier. Okay. Now, why the controversy? So what is this controversy? So for years and years, I'd say for decades uh I've worked on both sides of the Atlantic, both in Europe and in the United States. And for decades, there has been this battle and the battle or this battle, this uh intellectual discussion has centred around what is the best fluid to use if you're resuscitating someone? Is it to use crystalloid or Steve's keloids? Now, for decades, the Americans have said, and the Swiss, by the way, they have said crystalloids is the best because it's inexpensive. It's not allergenic. It's um it's uh readily available and yes, you need more of it, but that's okay. And the Europeans on a whole, mainly by the, not only but much, much of it was led by the Brits British was that colloid gives you more bang for your buck. So in other words, you don't need four leaders of crystalloid to get the equivalent of one leader colloid there. Therefore, if you want to resuscitate someone quickly, then use colloid. And this debate went on back and forth. The Americans would say, well, when you look at outcome studies, there's no difference and the Europeans would say, but it makes more sense to use colloid and it's biologically plausible. So this went on for decades. And then I think it has to do with the wars in hot countries like Afghanistan and Iraq that the soldiers had to carry all this gear and fluids. And the American military then said, well, you know, maybe it is better to carry less, you know, less volume because a theater is a kilogram. Hence, they suddenly understood how important collards were great. So the Europeans have one the controversy but suddenly, and I have no idea why this happened. But the Europeans suddenly re examined the effect of keloids and said, you know, we are, we don't think keloids do what they say on the tin. If you give a leader of keloids, it doesn't seem to improve the volume as much as we thought it does. It's not a leader or even close to a leader. It's pretty much similar to crystalloids. So they swap sides now. So now it's the Europeans were pushing for keloids, crystalloid, sorry. And the Americans are pushing for keloids. So what's going on? Why was this controversy? And I think this is what the cause is. It's not just me, by the way, this is the authors of this paper agreed. So let's look at the percentage of volume that's retained in the intervascular space if you give a leader of either crystalloid or colloid. So Ringer's lactate up in this experiment was about 20% and I said it was about 2025% of a crystalloid stays in the intervascular space. Now, if you look at um keloids in someone who's had blood volunteer taken off of them and then they've been re infused with a Cold Lloyd. So they are normal vel emmick and their chemo diluted, but they're normal bulimic. That's the key word. You can see it's close to 90% in both forms of keloids, which means that's pretty close to what the original theory was fine. So everything's pretty good so far. But if instead of taking blood off of volunteer and seeing how much of the coed stays in the intravascular space, you were to just fill them and not take blood off first. Now they're hyper of Olympic. So you have two different categories. You have one group of volunteers who are normal limit because you've removed blood and then given them fluid and the other group have not had blood taken off their hyperbole nick. They, they've been volume loaded and what, let's see what they look like in this case that not that far off of say 25 30% or so of the colored stays in so much less than in the normal limit group. Hence the group saying that keloids don't really do what they say they do. We're looking at the group on the right, the hyperkalemic group. Now, why would this be why this difference? Because when you overload someone with fluid, you have a neuro hormonal system that tries to protect your volume status. And we know that if you're lacking in volume, you have three hormonal systems sympathetic, the ras system and a DH we talked about that, we talked about hypernatremia. But if you have too much wrong, you have one system because you don't have that very often. I presume. So you don't have as many defenses against this. And the one system you have are the natural attic peptides or A and P. Okay. So what is a NP? There's also a brain natriuretic peptide. So it's, it's when the, when the heart, the venture for the atrium are stretched by too much volume, they released this peptide called naturally peptide. And that naturally peptide will vasodilate and cause a diary sis. But I also do a third thing and I'll show you this one in the second. So it's a cardiac hormone released by acute volume load. So what does it do? There's a normal electrical x that we just said was absolutely vital for many functions, by the way, not just for maintaining the volume status in your intervascular space, but we're talking about that specifically right now. So that's a control and this is a, an animal model. And you can see the Glycolax there after you've infused competent amp and it's totally destroyed the Glyco Calix, hence the fluid you give now will leak out in some ways. It's kind of logical because if you have too much volume, sorry, if you have too much volume, then you have to get rid of it quickly. Well, if you destroy the barrier, you're going to get rid of it, you're going to dilate and you're going to get rid of it. In fact, in heart failure, they use something called the serotype, which is a recombinant H and P which tries to make space for people out of heart failure didn't really work well as a treatment. But the idea was the same. So you can see that maybe the reason this controversy, whether crystalloid your colleagues actually do what they say um respect of college do they do what they say may well be because of the model they used and they gave volume two volunteers who are overloaded had a and P strip the glycolax. Hence they leaked out. Hence, of course, they don't, it doesn't stay in the intravascular compartment. Okay. So let's let's change gears now and let's um look at a little bit of history of flutes. So what does a teakettle have to do with fluid resuscitation? Well, if you live in London, at least they have uh you can get something called lime scale. If you look at your tea kettle or inside your tea kettle, you'll see there's this build up of lime scale. Now, why is that important? Because the solution that we use most often uh is what we call ringer's solution. It's one of the first ones. It was not the first solution after Saline. Now, why did that come about? Because a man named Sidney Ringer in London, who was a clinician and a pharmacologist was working on the contractile properties of the heart. And he was looking at the effects of various electrolytes on cardiac and involuntary muscle. And accidentally his technician mixed some of London tap water with the bath water that was surrounding the heart and being a an astute observer. Instead of firing his technician for ruining his bath. In his experiment, he noticed the heart muscle is contracting a lot stronger. And what he surmised was that it was the salts of sodium potassium, calcium, calcium chloride, a lime scale that in in these concentrations caused the heart to contract stronger. So he realized the importance of other electrolytes and not just salt, which is at a cl. Now, the next solution you probably have heard of is called Hartman's Solution. And heartburn was a pediatrician in the United States and he would try and resuscitate Children. This is the days before insulin was discovered in the 19 twenties, I believe. And what he did, what he noticed is that with these young kids coming in with uh with uh diabetic ketoacidosis required lots of saline as you know, and as he resuscitated these patient's, these kids, they would develop an increasing acidosis using normal saline. And what he surmised was that um the problem was that NACL has too much chloride relative to sodium. So there's no difference between the two. And if you recall when I gave you a lecture on acid base uh methods, acid based analysis, we talked about something called a strong iron difference and sodium chloride. And that would saline has absolutely no strong iron difference there's no difference between the sodium concentration and the chloride. It's, they're equal because it's salt. You throw it in a boil a pot of water and it dissolves into N A and see how equal amounts. So there's no strong iron difference. Hence what he realized was that by, by giving lots of saline because I give large quantities for these Children, you're going to get an acidosis. They called today uh hyperkalemic acidosis. I would prefer the term a strong iron diff acidosis because if you get someone half normal saline, you still get the same acidosis because there's no difference between the positive and negative ions. So what he did was he added a replacement to the chloride that was lactate. So he called it lactated ringers or Hartman's solution for the same because he said you need proportioning more sodium than chloride to avoid the SAS ido sis. Hence, he's increased. He's created a strong iron difference, but it's lactated, it's lactate replacing some of the chloride, hence, lactated ringers or heartburn solution. Okay. So let's look at types of fluids now. So which fluid? Well, we have lots of different types. So, crystalloid is basically water with salt and various proportions. So if it's got just sodium chloride, that's saline. If you have a lactate, replacing some of the chloride, that's ringer's lactate or heartburn solution, plasmalyte has different elements, different um an ions to replace some of the lactate. So instead of lactate, they use gluconate, natpe acetate. So they're various uh mixtures or you can use keloids and keloids are historically made up of various elements. Some of them are very surprising. I find you can use starches, we call his head of starches and that's made up of corn or uh potato. So it's basically um uh digested by bacteria into large molecular starches. The macro molecules. Hence, they're like keloids or dextran, which again is trigger that's been digested by lactate, uh producing bacteria or gelatin. So you take a beef gelatin and you boil it down and you um you can succinate it or your use your real link gelatin. So the various formulations of all these different elements, but the good news is I wouldn't worry too much about them because we're not using them very often because there are lots of different problems that I won't go into right now or the probably the most frequently use colloid in practice today, given the problems we have with these other elements is album. So if you're going to use a Crisp Lloyd, should you use State Line or Balanced Solutions? And this is a big debate and there've been many studies and to be quite frank, most of the studies are not really overwhelmingly impressive. And the there are pros and cons and they're really, there's no smoking gun, there's no really one study that's a killer study says, okay, we now know what you have to use. So let's look at this. Let's look, first of all, let's look at the components of these various uh solutions. Now, I don't want to read every element to this table because it's quite long and involved. But I will comment on one or two things. So if you look at the solution, the amount of concentration of sodium chloride, the strong wind difference, remember the strong differences, the difference we talked about this in our acid base talk, it's a difference between the sodium concentration and the chloride. That's actually it's positive and negative lines. But most of the sodium and most are chloride. So I want to make things a little bit simple. So just say sodium chloride and normally it's about 40 the ph the asthma lower osmolarity, the potassium lactate calcium and then some comments. So saline, as we said, 0.9 or we call normal saline has got 100 54 million moles of sodium and 100 54 moles chloride. Hence, there's no difference between too strong and differences. Zero. If I gave you glucose 5% the same thing would happen. It's zero piotre acidic um osmolarity, osmolarity is 308. Now, normally the asthma Larry's about 2 85. So that's kind of hyper asthma. It sorts hypertonic if you like. Uh there's no, so there's no potassium lacked in calcium and because of its higher osmolarity, it's probably the fluid of choice if you have some with a acute brain injury, say traumatic brain injury because you don't want the cells that are already going to be swollen to swell more. So if you can sort of shrink them slightly. And in fact, if we have some with a very swollen brain, we use hypertonic saline, which is about 3% saline. But in someone who's got a swollen brain or may have a swollen brain, that's a very good compromise. So you want to use something that's a little bit hypertonic. Uh The problem is, well though, as we said, if you give very large volumes and some experiments have shown you need about 12 leaders before you start getting a serious acidosis. And even that acidosis is not even sure whether that really causes problems or not. So we talk a lot about hyperchloremia acidosis with lots of same on and don't forget you need lots of same one. But even if you get that, it's not even sure that that makes a difference to outcomes next apartment solution or ringers like tape. Now we've done is we've made a difference between the sodium and chloride. So instead of 1 50 for sodium have 1 31 but the chlorides much difference and you have a difference between the sodium and chloride, unlike the saline and you fill the difference with black tape. And that means you now have a strong mind difference. It's not zero but 24 that's better. You're osmolarity is lower. So with uh brain injury, I'm not sure that'd be the ideal solution to use. Um but we've reduced the chloride lobe. That's the key thing. Ringer's lactate. Um which again is another form apartment. Uh It's pretty similar and plasmalyte is the one we use most often today because it comes closest to really mirroring your normal serum. And you've got strong difference of 40 which is exactly what we said was the normal strong difference. Hence, of ph of 7.4 that's normal. Instead of using lactate acetate gluconate are used. Now, does this really make a difference to outcomes? I'm not sure. I don't think so. And from everything I've read and everything I've seen not very impressive, but that's what we use because it biologically is plausible. So what does Saline actually look like? How much salt and saline? Well, in the real world, best thing to do is look at something that you actually eat every day. And if you're going to make a leader of saline, 0.9% sodium chloride, that's nine g per liter, 0.9% normal saline, you need about 50 bags of lay's potato chips or any potato chips. In fact, so does it really matter if you use saline balance crystalloids? Well, this is the Cochran study and you know, Cochran looks at all the evidence and almost invariably says we need more studies. But what they said was basically, they couldn't really find a major effect in terms of preventing in hospital mortality when you compare the two and in terms of kidney injury. Now, those that propose that we use um non saline crystalloid, a balanced crystalloid, we call it whether it's Hartman's or plasmalyte ringers like tape is, the high chloride concentration can cause uh glomerular vasoconstrictions of the Afrin arterial. So basically, you're reducing your glomerular filtration rate and that may cause renal damage. Now, that's very experimental and you need a lot of saline to get to that point. But you know, there's a theoretical possibility that you may get a slight increase in kidney injury. But in this study, this is a study of studies, they couldn't find very much evidence for it at all. And if there was evidence, it was very well and there's something I referred to before and I referred to one or two times in this lecture, there's something called a surviving sepsis campaign, which is a group of the world's and the experts who are on hold, give opinions on what they think we should do and they provide guidelines and I personally am not a slave to their guidelines, but it's a good starting point. And what do they say? They say we suggest using balance crystalloids instead of saline and it's not a very strong suggestion because as I said, the evidence is not fantastic and they say it's a weak recommendation because the evidence is low. So if I had Saline I would use Saline. If I had a traumatic brain injury, I would definitely use Saline. That, that I would say is clear that you use Saline. But for everything else, if I had Saline, I would not stop using Saline. But if I had a choice at hand, I had crystalloid that say plasmalyte or Hartman's and Saline, I might use uh balanced solution instead of Saline, but not without a lot of, a lot of uh strength of opinion. Okay, let's look at the color you've got. Now, as I said earlier, we have different types of start of solutions of which gelatin deck strands and starches and starches were the most popular artificial color codes and they were made of potatoes and corn and they were made to macro, they were obviously chemically modified, made into macro molecules. But for years, um we were using these solutions, something called head of starches. And again, there was a lot of debate whether they were safe or not and the number of publications proving they were safe, we're quite numerous. Hence, we used them quite often, especially in the operating room but also in intensive care and in resuscitation accident emergency. Well, it turns out the reason that there was such confusion and the argument for the safety and the efficiency or the efficacy of start solutions was from a surprising source. What was it? So they have debates, had massive debates about whether they were worth using or not. And they had one called the big debate. It's called the moral Maze. Should head head of starches, in other words be used at all. So this is a major debate and why did this debate come about because of this man? This is a German professor named Jacome Bolt. Professor Bolt. And he published 90 plus papers proving that these were good solutions, effective and safe. The only problem is that it turns out due to some sleuth work, some detective work that he made up all these research results. He's lied and he was the main advocate who had a lot of scientific clout. He was very respected because of all his studies. And in fact, his studies were made up amazing and his studies, if you removed his studies from the from the uh the the total body of work, looking at the safety and effectiveness of starches, and you take away his studies that are tainted by being dishonest. You now see there was a significant increase in mortality. So Mr Professor Bowl ended up in prison for his lies, which is a really a really a really earthquake. And by the way, it's not the first time that a well known medical scientist has been found to make up uh results, not often I hope but it's not unknown. So let's look at the main color that we would use today and that's album. So the starches and the gelatin and the deck strands I think you can probably, the starches maybe used, definitely not using intensive care anymore. You maybe use them in the operating room. Um That's a little bit debatable still. But I think the main one we talk about today is Albumin and Albumin is not just about volume. Yes. So it's a colloid. It's a good volume expander, but it's not just volume has a lot more to it than that. So it protects the Glyco okay, Alex. So not only is it doesn't require the Glycolax for it to work. We just saw that earlier, but it protects it at least in animal studies, not certain like a Calix, it's an antioxidant. Your body's natural, one of your body's natural antioxidants, it's anti inflammatory. It's a major binding protein. So it will bind endogenous compounds like Billy Ruben and Yulia and others, it improves drug delivery. So if you have to give someone a diuretic like a frusemide, it will carry that cruise mind to the Nephron, it reduces toxicity. So if you give someone Finney tone and you have less album and there's more free fenny tone, hence, more free talks uh free if any tone equals more drug toxicity. Also, it's a negative acute phase protein. That means if you are severely ill, almost immediately, your album will drop. And so it's uh if you are, if you're very ill in the intensive care unit and you have a normal albumin that hasn't been replaced, then you're probably not very ill. It's a marker of malnutrition. It's a marker of your severity of disease because of the negative acute phase protein. And it's a marker of mortality, lower the album and the more likely you are to die. What about the metabolism of album? And I just want to briefly go over this just to remind you. So you have intra vest your albumin is about 3.5 to 5.5 g per 100 MLS with a total body album of about 500 g. You synthesize synthesize in the liver about 15 g a day. And when you're very ill, your synthesis reduces somewhat, but it can increase two times if it's needed. You lose album in normal, you degrade about the same number of 15 g a day, but you can lose it in the V I tracked in the kidneys. For example, with nephrotic syndrome and burns, you have a flow of, of men. Normally, that's what we call the trans capillary escape rate. About 5% an hour is removed from the intravascular compartment to the interest Ishan, but it then recirculates through the lymph to back to the intravascular compartment. So it's got a continuous cycle and the t er the transcript escape rate will increase, especially if you have inflammation, sepsis, trauma of any sort. And that depends on the integrity of the Glaxo cakes. What about its intravascular effects? Well, we said earlier about keloids versus crystalloids if you look specifically at uh Ringer's lactate, for example, after hemorrhage and you replace the blood that's lost with Ringer's lactate. What's the volume effect there? You have Ringer's lactate. And we said that keloids would be greater in someone who's lost blood. So we're not making someone hyperbole Mick. Now, uh they're replacing the lost volume. Well album in 4% which is close to your natural concentration of albumin is much greater if you give 20% and we do that more often in small volume. So 100 mils of 20% for example, you can see that in hemorrhage and sepsis, you're going to get a much greater volume effect, giving a smaller volume. Of course, you're giving say 100 mils and you're placing a lot more of that willingness loss compared to wring his leg. So it's a good, it's got a good volume effect, especially the 20% so concentrated album. What are the use development? Well, if we summarize what we know about album today, the evidence we have for that we know that you will cause harm or there's no evidence for its use if you have extraperitoneal infections and liver cirrhosis. So I have liver cirrhosis and you'll see in a second because liver cirrhosis is often associated with giving album and it has some very well um well um known positive effects in cirrhosis but not an extraperitoneal infection. So, if I have pneumonia, for example, there's no point in giving me albumin because I have cirrhosis and, and, and uh pneumonia, hence an infection outside the peritoneal. But most importantly, if I have an acute brain injury, now album has been shown to be harmful in acute brain injuries. And the main reason for that is that in the formulation that was studied in this famous study called the safe study, they used relatively hypotonic album. So compared to Saline, we saw earlier, it's got a higher osmolarity which will not cause the brain to swell more with the albumin, which is relatively hypotonic that will cause the brain cells to swell more. So you don't want to use album and if you have an acute brain injury, you don't wanna use Saline. What about possible evidence is still coming in? But it's not, it's not a smoking gun. E it's not 100%. Well, if you have someone who's not passing urine, you want to get rid of some fluid and you give them diuretics and it's not really doing the job, especially if they have a low albumin. So they're hypoalbuminemic. You give diuretics and albumin and as I said earlier, albumin will transport your, your diuretic to the tubules. So it will cause a larger increase of diaries. So it's good to give that especially 20%. Um If someone's hypoalbuminemic and they're not responding to direct cardiac surgery, it seems to have some positive effects and sepsis, maybe recommended. This is where the evidence is much stronger if you have sepsis, resuscitation. So someone's got sepsis and you start giving them large quantities of crystalloid, which is the recommendation today. The evidence isn't fantastic, but that's what we do. You give them large volumes and they're still not responding, then you might want to consider giving album in because you're gonna get, you'll need less volume. So you don't want to give somebody way too much volume. So start off with crystalloids and if they're still not responding after a couple of leaders, you might want to then consider giving out. Now in the cirrhotic patient has said above where you do have evidence. If you have someone with the hepatorenal syndrome or someone with spontaneous bacterial peritonitis, albumin is definitely recommended also again with a scerotic patient if you're taking off lots of acidic fluid, so you're using, you know, have large volume parasynthesis, you want to replace like with like, so you want to, if you lose, if you take say five liters off, you're going to give the equivalent of five liters of album. And if you have someone who's going to be ultra filtrated, so they're on a dialysis machine and they're going through ultra filtration, they're getting renal replacement therapy and they're hypoalbuminemic, you'll often get what they call dialectic hypertension. So when you put them on the machine, they immediately drop their BP, which is not a good thing. You give them some hypertonic album in uh you know, 20% and that will uh prevent or diminish the drop in blood pressure when you hook them up to a uh renal replacement issue. And that's got good evidence to it. And just to summarize the surviving sepsis campaign says we recommend against starches. So in itu this is no starch theater me a little bit less pure, but I think most people stay away from it. Now, the evidence is strong and the quality of evidence. So the recommendation is strong and the quality of evidence is high using albumin. When you had large lines of crystalloid, as we said earlier, the evidence, the recommendations week because the evidence is moderate just to keep in mind cost. By the way, it's one of the reasons people are not too excited about getting some of these fluids and you have to bear this in mind because we do use them a lot large quantities you here. So if you look at the fluid and the cost per leader in dollars, Saline's about a dollar a liter, Hartmann's pretty similar plasma-lyte twice the price. But again, the evidence that it's actually better than Hartman's or even Saline isn't fantastic. It is biologically closer to a normally um constituted serum, but that's, you know, theoretical in some ways. But the price is a little bit more expensive albumin much more $65 that's quite a bit more, 30 times more. And then if using red cells is to give you an idea of how much they cost. That's about $345. So you can see that there's a lot of money involved here, but we don't give that much in the way of red cells. Luckily, so some practical matters of fluid and future. Um, I think this is something that's, uh, worth focusing on for a few minutes. So, how many times have I seen somebody come up to me and say, can you put a central line in for my patron? And I'd say, yeah, certainly why I'm not a technician. I want to know why you want a central line. What's your indication? And the number of times a doctor would ask me to put a central line often, you know, a medic on the wards, word surgery. They'd say, well, because we think we, they may need fluid rapidly is not smart. So they want this because they think they may need fluid rapidly. And I would say, no, you don't want that. I may want to, you may want a central line for a good reason, but that's not the reason. That's a, that's a stupid reason. This is what you want. So for example, when I work trauma in the United States, in the second largest trauma center in the States, and maybe the world, if someone needed fluid rapidly, they put in very, very short, very fat iv's into your anti cubital fossa. So they didn't put a central line in for that. And why? Because we're working with processes processes law okay. The flow is determined by the radius of your, of your cannula to the fourth power. So if you double it, it's two times, two times, two times two, that's 16 times. And for whatever the same pressure gradient is, and it's divided by the length. So the longer it is the less flow it is and it's proportional. So if I double the length by half the flow, so radius is the big player and the length is inversely proportional. So I want short and fat and of course viscosity as well. So a 20 centimeter, a central line is not the best way to get fluid rapidly. And that's ironic because so many times I get asked or you'll be asked to put a central line in and say why? And if they say it's because I want to get fluid quickly. Well, you say you better go back to the books because you don't know what you're talking about. It's very common, too afraid. So short and fat is best, especially fat in this case that I mean by the large diameter of your cannula. So look at the flow rates here, that's 22 kids. It's a blue Cannula, you're putting it okay. There's your flow not very good. Here is a 16 gauge Cannula, you can go lower, you can go 14 and even 12 gauge. Let's say 14 gauge. Is that really the communist intravenous cannula you can use. And if you increase from 22 to 16, you get a 390% increase in flow with 100 and 30% increase in diameter. So you get much greater flow with a bigger Candida so short and fat. And I said short because if you look at this is the same diameter can, you'll 16 gauge is a five centimeter 14 centimeter 30 centimeter. You can see that the flow is much greater in the shorter cannula, so short and fat. Okay. Clinical case. This is another common mistake. We see this was a true story. I remember very well. Saturday morning, I was walking into the obstetric unit and there were two consultants who were milling around a woman. They asked me to come and see her. She had given birth to a baby, a healthy baby and she was a healthy woman a couple of hours earlier. She had been found collapsed on the bathroom floor, ok. Delivered a healthy baby boy a term three hours, two or three hours earlier. Her BP was okay. Heart rate was not too bad. She was awake uh but they were worried, you know what's going on here. And they said, well, she couldn't have bled because her hematocrit was unchanged at 39%. So she hadn't dropped her hematocrit. They were looking for blood loss by looking at the hematocrit and I said, when I heard that, I said, you know, that doesn't really work because does this really exclude an internal bleed? They said, well, it can't be an internal bleed because your hematocrit is to stay well. Is that true? So let's look at this is, this is a blood volume, okay. There's your mad acquits the percentage of cells to plasma. In this case, it's 45% that's normal hematocrit. If I suddenly bleed and my blood volume is reduced to say, I don't know, 60% 50% of what it was normally. So if someone's just had a major bleed, say it abdominally or introduce a gastric lee, they're hematocrit, the percentage of red cells to plasma will be pretty much the same. So looking at hematocrit as a as a measure of blood loss doesn't make sense. Now, if I resuscitate you because you're dropping your BP, I'm not going to immediately give you blood. The first thing I'll probably give you is a cell, your fluid, maybe Hartman solution. Now, in this case, if I give you Saline, for example, or Hartman's or whatever a cell, your fluid. In other words, self fluid that doesn't have red cells. Now, I'm going to dilute that same quantity of red cells and now my hematocrit is going to drop. So that may be a reflection of me resuscitating you. And if I give whole blood, well, I go back to normal. So what I'm saying is that if someone says always had a gastric bleed and you want to know is he still bleeding? Because sometimes what doctors often do is they keep repeating. Humana quits. Well, as if, if no extra a cellular fluids been given, then your hematocrit will not change dramatically. So you can't really use that in itself as a marker of uh of hidden blood loss. And in fact, the I asked the consultants to do an ultrasound, they got someone to do it cause they didn't know how to surprise me. And he had a major bleed into her broad ligament. So even though she had a normal issue, hematocrit, she did have a bleed, okay. So this is something I think I heard you earlier, we know that if someone has um trauma and becomes hypovolemic, you will almost, and you have a cardiac arrest, you will almost always die okay. And that a CLS says we could rapidly infuse if someone's uh let's do this again. So someone who's hypothalamic after trauma needs a rapid in future and they know that traumatic cardiac arrest due to hypovolemia is almost always fatal. Why? Well, let's look at this. If you have someone who's been traumatized, it's severe enough to cause a cardiac arrest, you've lost more than 40% of your blood volume. And that's considered a class four. It doesn't matter the numbers, you know, to memorize those, but it's severe. 40% of your blood volume has been lost. That's equal to two greater than two liters of your five liter blood volume. Okay. That's a lot of blood to lose. And that could cause you to have an arrest. So let's say they say you could treat this by quickly infusing fluid. So we're gonna put fluid in rapidly. So let's see how fast food to go in. If you can use gravity. If you happen to have a rapid infusion device, which most people will not have immediately present, you can set one up. But that takes time. If you just pour fluid in, you're gonna get a maximum flow of about 100 mils a minute. That means if you've lost over two leaders, you're gonna need over 20 minutes to fill that space up. That's way too long. So what should you do? Well, how about this? You can raise the legs. If you raise the legs quickly, you will transfuse or auto transfuse of the order of 300 mills or more of fluid. Not head down by the way, because for reasons to do with your intrathoracic pressure that we talked a long time ago. Remember those bags of let this, that I told you about transmural pressure. I haven't got time to go into this, but basically it's legs up, not head down, legs up, give you a rapid transit auto transfusion and then you carry on giving fluid yourself. I'm not saying not to get fluid but you need something quick and that's probably the best way to do it. So to recap, we've talked about the most important thing is not blood, it's blood volume. You want to know the physiology of where fluids go. Hence, you understand why we use different fluids for different situations. You want to know a luga about the importance of the Glyco Calix in maintaining the intervascular integrity of fluids and how that can be destroyed by over film, you know, different types of fluids, difference, crystalloids and their various form formulations and keloids. And today we use mainly album um we saw about the different volume effects of different types of albumin compared to crystalloids, 20% being even greater than 4% but you need less volume for the same effect or even greater effect. We want to use a short and fat. Um Can you like if you're gonna get fluid rapidly and you don't need a central line, you couldn't even use a central line for rapid fluid infusion doesn't make sense in terms of physics, um adequate as a marker is not a great marker if you think you may have blood loss, unless someone's been getting fluid to try and maintain the BP, that therefore you're going to be seeing the effects of resuscitated fluid, uh which will dilute your blood. But in terms of not, you know, absolute volume being lost, you're not gonna see much of a difference. So it's not a great marker. And if you ever need fluid rapidly while you're, you know, setting up an infusion, just raise the legs. And that is really it. So if you have any questions, I'd be happy to try and answer them. Uh Could you explain that uh crystal was this colloid uh in a hypo and a high pollen and uh that graph you showed? So sorry, I didn't catch that. Could you repeat that again, please? Uh There was a graph you showed regarding Crystal Lord was his school ord uh in hyperkalemic and a hyperkalemic condition. Could you show that again? Yeah. So, so what I was saying was that there's been endless debates that quite frankly uh you know, we you could, you could spend the next 30 years debating this and people have and there's been studies coming out and they show a little bit of a, a difference, no difference. And this, you know, everyone's using the evidence, the imperfect evidence they get to defend their position. And what I was saying was that the most likely cause of this confusion, why they people don't agree is because by giving volume to a volunteer, what you're trying to do is say, I think keloids do not do what we think they do. I think if you give me a leader of colloid, I will not have close to a leader that stays in my intravascular compartment. That's my opinion. Okay. That's not, that's I'm pretending I'm an advocate. This and the reason might be is that when I did my study, where I looked at a study, what they did was they gave a leader of coal oid to somebody who has is normally has a normal volume. So what you're doing, you're adding another leader on, you're making them hypervolemia like not normal bulimic. And by making them hyperkalemic, you release a MP because your heart's being stretched and that will destroy your Glyco Calix. As you saw that electro micrograph and that will cause the coma to leak out because you need a glass. Okay, Alex for cold had to stay in, into a vascular. Uh It's uh in fact, in the real world, why would you give somebody a keloids when they've lost blood? So most of the time you're not getting volume to someone who's hyperbole that you're giving to someone who's hypovolemic. In this case, it seems to work. That's why I'm just saying you're comparing apples and oranges. It's an experimental uh misunderstanding, I think. Yes doctor. There's a question here in the chat. Why is colon preferred in the peritoneal disease? Is it's not, it's not preferred in perennial disease. It's preferred in cirrhosis where you have uh intraperitoneal um infections. Uh It's a little bit complicated. Don't, don't forget it's not colloid, it's Albumin's okay. So it's album we're talking about and don't forget a couple of things. Albumin has got a lot of effects that first of all, the liver produces albums. So if you have a sick liver with cirrhosis, you're almost invariably going to have a low albumin and albums got a lot of effects that are important antioxidant, anti inflammatory. But also it um we talked about effective arterial blood vine in the past. And what probably happens is that you have basically an empty effective arterial blood vine in your thorax where you have your stretch receptors. And I presume by giving album and you're filling that up again, it's a little bit complicated, but basically the evidence is very good for that. So that's what I would use in those cases. All right. Thank you. Is there any more of the questions for the doctor Mr Doctor? There's another question, what fluid is more preferred in shock? Uh Well, as I said, what you probably use initially is crystalloid. Um I think it's the general consensus without a lot of very, very, very hard evidence. But the general consensus that you start giving crystalloid, give a few leaders. And if you're still not getting the results you're hoping for, then you might add some album in. And of course blood, if there's blood loss. Thank you. And I do say like if I had Saline, I wouldn't, if I, if I had a choice between, if I have two bags, Saline and a balanced solution, I'd probably go for the balance solution. But if I didn't have a balanced solution I just go Saline. I mean, there's not a lot of evidence that you know, that one's good and one is bad for you, but a lot of this stuff has got, hasn't got a lot of really hard evidence. That's what I'm saying to you. So, you know, okay, um, if there's no other questions for the doctor, I think that should be all for today. Thank you very much again doctor and I thank everyone for attending and um yeah, I have a lovely, have a lovely day. Okay. All right. Take care everyone. Goodbye. Goodbye.